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| 1.
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Murono, Shigeyuki ; Yoshida, Hiroshi ; Kobayashi, Tetsuro ; Kawase, Tomotaka ; Kikuchi, Daisuke ; Suzuki, Toshihiko ; Nakanishi, Yosuke ; Endo, Kazuhira ; Kimura, Hiroaki ; Wakisaka, Naohiro ; Yoshizaki, Tomokazu ; 室野, 重之 ; 中西, 庸介 ; 遠藤, 一平 ; 脇坂, 尚宏 ; 吉崎, 智一
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金沢大学医薬保健研究域医学系<br />Background: Multifocal human papillomavirus (HPV) infection into the palatine and pharyngeal tonsils
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, which might be linked to a second primary tumor of HPV-positive oropharyngeal cancer (OPC), was investigated. Patients and methods: One hundred and five patients with various head and neck diseases including 14 patients with OPC were enrolled in this study. Swabs from the palatine and pharyngeal tonsils were collected in each individual, and auto-nested GP5+/GP6+ PCR for HPV DNA was performed. Results: HPV DNA was detected in the palatine tonsil or the pharyngeal tonsil in a small subset of upper respiratory tract cancer other than OPC (URTC) and non-cancer diseases. Furthermore, HPV DNA was detected in both the palatine and pharyngeal tonsils in the same individual in 2 of 48 (4%) URTC cases, and 1 of 43 (2%) non-cancer cases. On the other hand, p16-positive OPC cases demonstrated a higher HPV DNA detection rate (4 of 9, 44.4%) compared with other disease groups. Conclusion: HPV DNA detection in both the palatine and pharyngeal tonsils in the same individual, especially in HPV-OPC, suggested the ability of HPV to infect tonsillar tissues of Waldeyer’s ring multifocally. © 2017 Acta Oto-Laryngologica AB (Ltd)<br />Embargo Period 12 months
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| 2.
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Nakanishi, Yosuke ; Kondo, Satoru ; Wakisaka, Naohiro ; Tsuji, Akira ; Endo, Kazuhira ; Murono, Shigeyuki ; Ito, Makoto ; Kitamura, Kouichi ; Muramatsu, Masamichi ; Yoshizaki, Tomokazu ; 近藤, 悟 ; 脇坂, 尚宏 ; 辻, 亮 ; 遠藤, 一平 ; 室野, 重之 ; 喜多村, 晃一 ; 村松, 正道 ; 吉崎, 智一
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金沢大学医薬保健研究域医学系<br />Purpose:In humans, activation-induced cytidine deaminase (AID) expression results due to inflammatio
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n and this deaminase activity is also involved in carcinogenesis. The aim of this study is to investigate the correlation between AID expression and the clinical classification of oral cancer tissues.Experimental Design:The current study investigated the correlation between AID expression and the clinical classification of oral cancer tissues from 27 patients who underwent surgical resection using immunohistochemistry. Specific AID expression and its induction by cytokine stimulation were investigated in cultured HSC oral cancer cell lines by reverse transcriptase PCR.Results:AID expression was detected in 10 of 27 specimens (37.0%). AID expression was more frequently detected in early-stage cancer, especially in early stage T, than in late-stage cancer (T1/T2 vs. T3/4; P = 0.0493, N0 vs. N1/2/3; P = 0.0793). HSC-2, a nonmetastatic oral cancer cell line, abundantly expressed endogenous AID, whereas no such expression was observed in HSC-3, a metastatic oral cancer cell line. Moreover, AID expression was substantially induced in HSC-2 cells by stimulation of an inflammation-related cytokine, TNF-α.Conclusions:Aberrant AID expression in the oral epithelium would contribute to the initiation of oral squamous cell carcinoma. Avoiding persistent AID inducible condition such as frequent cleaning of oral cavity would play an important role for the prevention of developing oral cancer. © 2013 Nakanishi et al.
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| 3.
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Seishima, Noriko ; Kondo, Satoru ; Wakaea, Kousho ; Wakisaka, Naohiro ; Kobayashi, Eiji ; Kano, Makoto ; Moriyama-Kita, Makiko ; Nakanishi, Yosuke ; Endo, Kazuhira ; Imoto, Tomoko ; Ishikawa, Kazuya ; Sugimoto, Hisashi ; Hatano, Miyako ; Ueno, Takayoshi ; Koura, Miki ; Kitamura, Kouichi ; Muramatsu, Masamichi ; Yoshizaki, Tomokazu ; 近藤, 悟 ; 脇坂, 尚宏 ; 喜多, 万紀子 ; 遠藤, 一平 ; 波多野, 都 ; 小浦, 美樹 ; 喜多村, 晃一 ; 村松, 正道 ; 吉崎, 智一
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金沢大学医薬保健研究域医学系<br />Activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing catalytic polypeptide
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3 (A3) family are cytidine deaminases that play critical roles in B-cell maturation, antiviral immunity and carcinogenesis. Adenoids and palatine tonsils are secondary lymphoid immune organs, in which AID and A3s are thought to have several physiological or pathological roles. However, the expression of AID or A3s in these organs has not been investigated. Therefore, we investigated the expression profiles of AID and A3s, using 67 samples of adenoids and palatine tonsils from patients, with reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analyses. AID and A3s expression levels in the adenoids and the palatine tonsils of the same individual significantly correlated with each other. Of note, AID expression level in the adenoids negatively correlated with the age (r = −0.373, P = 0.003). The younger group with adenoid vegetation and tonsillar hypertrophy showed more abundant AID expression than the older group with recurrent tonsillitis and peritonsillar abscesses (P = 0.026). Moreover, immunohistochemical analysis revealed the distribution of AID and A3s in the epithelial cells as well as germinal centres. The localisation of AID expression and its relation to age may contribute to adenoid vegetation and inflammation.<br />Ministry of Education, Culture, Sports, Science and Technology B23390396,A24689064
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| 4.
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Wakaea, Kousho ; Nishiyama, Tomoaki ; Kondo, Satoru ; Izuka, Takashi ; Que, Lusheng ; Chen, Cong ; Kase, Kina ; Kitamura, Kouichi ; Md , Monjurul ; Wang, Zhe ; Ahasan, Md Monjurul ; Nakamura, Mitsuhiro ; Fujiwara, Hiroshi ; Yoshizaki, Tomokazu ; Hosomochi, Kazuyoshi ; Tajima, Atsushi ; Nakahara, Tomomi ; Kiyono, Tohru ; Muramatsu, Masamichi ; 西山, 智明 ; 近藤, 悟 ; 加瀬, 希奈 ; 喜多村, 晃一 ; 中村, 充宏 ; 藤原, 浩 ; 吉崎, 智一 ; 村松, 正道
概要:
金沢大学医薬保健研究域医学系<br />Mitochondrial DNA (mtDNA) mutations are found in many types of cancers and suspected to be involved
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in carcinogenesis, although the mechanism has not been elucidated. In this study, we report that consecutive C-to-T mutations (hypermutations), a unique feature of mutations induced by APOBECs, are found in mtDNA from cervical dysplasia and oropharyngeal cancers. In vitro, we found that APOBEC3A (A3A) and 3B (A3B) expression, as well as mtDNA hypermutation, were induced in a cervical dysplastic cell line W12 when cultured in a differentiating condition. The ectopic expression of A3A or A3B was sufficient to hypermutate mtDNA. Fractionation of W12 cell lysates and immunocytochemical analysis revealed that A3A and A3B could be contained in mitochondrion. These results suggest that mtDNA hypermutation is induced upon keratinocyte differentiation, and shed light on its molecular mechanism, which involves A3s. The possible involvement of mtDNA hypermutations in carcinogenesis is also discussed. © 2018 The Author(s).
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| 5.
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Wakisaka, Naohiro ; Endo, Kazuhira ; Kitazawa, Tomohiro ; Shimode, Yuzo ; Kato, Koroku ; Moriyama-Kita, Makiko ; Koda, Wataru ; Ikeda, Hiroko ; Ishikawa, Kazuya ; Ueno, Takayoshi ; Nakanishi, Yosuke ; Kondo, Satoru ; Sugimoto, Hisashi ; Yoshimura, Kenichi ; Tsujii, Hiroyuki ; Kawashiri, Shuichi ; Omoto, Kiyoshi ; Yoshizaki, Tomokazu ; 脇坂, 尚宏 ; 遠藤, 一平 ; 加藤, 広禄 ; 喜多, 万紀子 ; 香田, 渉 ; 池田, 博子 ; 石川, 和也 ; 上野, 貴雄 ; 中西, 庸介 ; 近藤, 悟 ; 杉本, 寿史 ; 吉村, 健一 ; 川尻, 秀一 ; 吉崎, 智一
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金沢大学医薬保健研究域医学系<br />Background: In sentinel lymph node (SLN) biopsy for head and neck cancers, the radioisotope method h
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as been the gold standard. However, this method has several problems, such as unavoidable radiation exposure and requirements of expensive equipment. Aims/Objectives: To overcome these problems, we evaluated the contrast-enhanced ultrasonography (CEUS)-guided SLN-detection method, and predicted the SLN metastatic status using novel ultrasound technology, superb microvascular imaging (SMI). Methods: Ten patients (6 with oral and 4 with oropharyngeal cancers) without neck lymph node metastasis were enrolled in this study. Ultrasound contrast agent, Sonazoid ™ , was infiltrated into the mucosa at the primary site to observe the lymphatic ducts and SLNs in the neck field. The detected SLNs were examined for blood flow using SMI to categorize the SLNs metastases-positive or negative. Results: SLNs were successfully detected in 8 out of 10 cases. In 7 out of the 8 cases, in whom SLNs were successfully detected, the metastatic status of SLNs was correctly diagnosed with SMI. Conclusions and significance: Although more clinical data are needed based on a larger cohort, establishing the CEUS-guided SLN-detection and criteria for the accurate diagnosis of SLN-metastases using SMI would be valuable as an alternative to radioisotope method, in oral and oropharyngeal cancers. © 2019, © 2019 Acta Oto-Laryngologica AB (Ltd).<br />Embargo Period 12 months<br /># This study was approved by the Bioethics Committee of Kanazawa University (Nos.2016-037 and 2017-015). The clinical study protocol was explained in detail to patients eligible for the study. Written consent was obtained from all patients who agreed to participate.# This work was supported by a grant-in-aid from The Public Trust Fund For Clinical Cancer Research.
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| 6.
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Toyama, Minoru ; Notoya, Masako ; Harada, Hiromi ; Nakatani, Ken ; Sugimoto, Hisashi ; Ishimaru, Tadashi ; Yoshizaki, Tomokazu ; 外山, 稔 ; 能登谷, 晶子 ; 原田, 浩美 ; 中谷, 謙 ; 杉本, 寿史 ; 石丸, 正 ; 吉崎, 智一
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Objectives: To examine predictors of syllable extraction proficiency, a prerequisite forchildren with hearing impairments progressing from spoken to written language by theKanazawa Method.Background: The rates of delayed language
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acquisition in children with hearingimpairments have remained unchanged despite increased use of cochlear implants. Childrenborn with hearing deficiencies do not receive sufficient auditory inputs, which contributesto delayed acquisition of spoken language. As spoken language is the springboard towritten language, such children are likely to experience delays in acquisition of syllableawareness and written language when taught in the same way as children without hearingimpairments. However, most research on syllable awareness in children with hearingimpairments in Japan is related to studies targeting school-age children and later. Therefore,it remains unclear how to manage syllable awareness problems in pre-school-age children.Methods: This study was conducted on 68 children with hearing impairments, between 4 and6 years of age, diagnosed by the Kanazawa University Hospital with congenital deafness beforethe age of 4 years and receiving outpatient language instruction. To examine the predictors ofsyllable extraction scores, we performed multiple-regression analysis with syllable extraction asthe dependent variable and age, unaided hearing level, and scores for remaining language skills(auditory word comprehension, syllabification, syllable extraction, written language characterrecognition, and written language sentence comprehension) as independent variables.Results: Stepwise regression analysis showed that written language character recognitionscore, age, and auditory word comprehension score contributed to the syllable extraction score.Discussion: The relationship between syllable extraction proficiency and age was consistentwith previous reports. Early intervention targeting character recognition and auditory wordcomprehension assisted the teaching of written language and improved syllable awarenessin children with hearing impairments. The results of this study indicated that early-stageintervention in written language character recognition and auditory word comprehension isan effective method of teaching children with hearing impairments to facilitate acquisitionof written language and the development of syllable awareness. The vocabulary and syllableawareness acquired by exposure to a combination of spoken language, Japanese sign language,and written language can be easily transferred to speechreading. Using the Kanazawa Methodto facilitate understanding of the structure of Japanese language can help children with hearingimpairments to acquire syllable extraction proficiency, regardless of their unaided hearing level.
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| 7.
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Uramoto, Naoki ; Furukawa, Mitsuru ; Yoshizaki, Tomokazu
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金沢大学医薬保健研究域医学系<br />The majority of the oncogenic osteomalacia-associated mesenchymal tumors are considered to belong to
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the category of phosphaturic mesenchymal tumors, mixed connective tissue (PMTMCT) variant, of which malignant cases are very rare. Here we report a case of a recurrent malignant PMTMCT variant which arose in the tongue. The patient was treated with surgery at an initial treatment and the first recurrence. In accordance with the tumor recurrence and resection, the hypophosphatemia progressed and improved. However, hypophosphatemia did not progress after receiving radiation therapy at the second recurrence even though the recurrent tumor gradually increased its size. These results suggest clinical feature of malignant PMTMCT could be changed by radiation therapy. Thus, this report could add an insight to the nature of PMTMCT. © 2008 Elsevier Ireland Ltd. All rights reserved.
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| 8.
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Sugimoto, Hisashi ; Ito, Makoto ; Hatano, Miyako ; Kondo, Satoru ; Suzuki, Shioto ; Yoshizaki, Tomokazu
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金沢大学医薬保健研究域医学系<br />Objectives: The authors recently demonstrated that extensive bone erosion correlated with a worse pr
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ognosis of the squamous cell carcinoma (SCC) of the temporal bone. The present objective was to investigate the expressions and the roles of epithelial-mesenchymal transition (EMT) in SCC of the temporal bone. Study Design: Retrospective patient file review and immunohistochemical study of tissues of patients with SCC of the temporal bone. Patients: The authors examined the expressions of vimentin in 16 patients with SCC of the temporal bone by immunohistochemical analysis. Results: As expected, vimentin was expressed on SCC of the temporal bone. We regard the patient who has vimentin-positive cells as EMT-positive patient because gain of vimentin is a hallmark in the EMT reported in several types of cancer. EMT positive tumors significantly correlated with extensive bone erosion, and extensive bone erosion correlated with a worse prognosis of the SCC of the temporal bone. Conclusion: The study results suggest that EMT in tumor cells becomes an important indicator of poor prognosis in SCC of the temporal bone. Copyright © 2011 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
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| 9.
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Sugimoto, Hisashi ; Ito, Makoto ; Hatano, Miyako ; Nakanishi, Yosuke ; Maruyama, Yumiko ; Yoshizaki, Tomokazu
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金沢大学医薬保健研究域医学系<br />Although it appears very uncommon in adult COM, Mycobacterium abscessus should be considered as a po
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ssible cause of a chronically draining ear. Multi-antibiotic chemotherapy including high-dose clarithromycin can effectively treat adult COM cased by M. abscessus. The first case report of adult chronic otitis media (COM) caused by M. abscessus is described here. A 61-year-old woman presented persistent otorrhea for 2 months, despite treatment with standard antimicrobial drugs. Physical examination revealed a small perforation of the tympanic membrane and edematous middle ear mucosa. Mycobacterial cultures and PCR yielded non-tuberculous mycobacteria (NTM); M. abscessus. Intravenous panipenem/betamipron and amikacin and oral clarithromycin were administered for 36 days. Computed tomography of the temporal bone showed improved aeration in the tympanic cavity, but soft tissue shadow remained unchanged in the mastoid 31 days after starting medication. She therefore underwent tympano-mastoidectomy at 36 days. At surgery, inflammation remained in the middle ear, and edematous pale mucosal tissue was noted around the stapes and ossicular chain. Histopathologic examination showed inflammation and granulation tissue, but no caseating necrosis or acid-fast bacilli. After surgery the symptoms resolved and remained well without evidence of infection recurrence 12 months after the operation. © 2010.
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| 10.
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Maruyama, Yumiko ; Arai, Kazunori ; Hoshida, Shigeru ; Yoneda, Kenzi ; Furukawa, Mitsuru ; Yoshizaki, Tomokazu
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金沢大学医薬保健研究域医学系<br />We report the first case of three delayed complications following irradiation for laryngeal carcinom
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a: bilateral vocal cord immobility, obstruction of esophagus and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial fixation of bilateral vocal cords and stenosis of cervical esophagus were noted at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging into the hypopharynx and obstruction of the esophagus occurred at 35 years after irradiation. The life-threatening hemorrhage was successfully treated by microcoil embolization of the common carotid artery. The relationship between these complications and irradiation is also discussed. © 2008 Elsevier Ireland Ltd. All rights reserved.
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